CHF is a debilitating disease in which abnormal function of the heart leads to inadequate blood flow to fulfill the needs of the tissues and organs of the body. Typically, the heart loses propulsive power because the cardiac muscle loses capacity to stretch and contract. Often, the ventricles do not adequately fill with blood between heartbeats and the valves regulating blood flow become leaky, allowing regurgitation or back-flow of blood. The impairment of arterial circulation deprives vital organs of oxygen and nutrients. Fatigue, weakness and the inability to carry out daily tasks may result. Not all CHF patients suffer debilitating symptoms immediately. Some may live actively for years. Yet, with few exceptions, the disease is relentlessly progressive. As CHF progresses, it tends to become increasingly difficult to manage. Even the compensatory responses it triggers in the body may themselves eventually complicate the clinical prognosis. For example, when the heart attempts to compensate for reduced cardiac output, it adds muscle causing the ventricles to grow in volume in an attempt to pump more blood with each heartbeat. This places a still higher demand on the heart's oxygen supply. If the oxygen supply falls short of the growing demand, as it often does, further injury to the heart may result. The additional muscle mass may also stiffen the heart walls to hamper rather than assist in providing cardiac output.
CHF has been classified by the New York Heart Association (NYHA) into four classes of progressively worsening symptoms and diminished exercise capacity. Class I corresponds to no limitation wherein ordinary physical activity does not cause undue fatigue, shortness of breath, or palpitation. Class II corresponds to slight limitation of physical activity wherein such patients are comfortable at rest, but wherein ordinary physical activity results in fatigue, shortness of breath, palpitations or angina. Class III corresponds to a marked limitation of physical activity wherein, although patients are comfortable at rest, even less than ordinary activity will lead to symptoms. Class IV corresponds to inability to carry on any physical activity without discomfort, wherein symptoms of CHF are present even at rest and where increased discomfort is experienced with any physical activity.
In view of the potential severity of CHF, it is highly desirable to detect its onset as early as possible. One technique for identifying CHF is to detect Cheyne-Stokes Respiration (CSR), which is an abnormal respiratory pattern often occurring in patients with CHF. CSR is characterized by alternating periods of apnea (i.e. a lack of breathing) and hyperpnea (i.e. fast, deep breathing.) Briefly, CSR arises principally due to a time lag between blood carbon dioxide (CO2) levels sensed by the respiratory control nerve centers of the brain and the blood CO2 levels. With CHF, poor cardiac function results in poor blood flow to the brain such that respiratory control nerve centers respond to blood CO2 levels that are no longer properly representative of the overall blood CO2 levels in the body. Hence, the respiratory control nerve centers trigger an increase in the depth and frequency of breathing in an attempt to compensate for perceived high blood CO2 levels whereas the blood CO2 levels have already dropped. By the time the respiratory control nerve centers detect the drop in blood CO2 levels and slow respiration in response, the blood CO2 levels have already increased. This cycle becomes increasingly unbalanced until respiration alternates between apnea and hyperpnea. The wildly fluctuating blood chemistry levels can exacerbate CHF and other medical conditions.
When CHF is still mild, CSR usually occurs, if at all, only while the patient is sleeping. Hence, the detection of CSR during sleep can be helpful in detecting the onset of CHF. However, CSR during sleep can also be caused by central sleep apnea (CSA), a neurogenic sleep disorder. When blood CO2 levels exceed a certain threshold, the respiratory control nerve center of the brain generates a burst of nerve signals for triggering inspiration. The nerve signals are relayed via phrenic nerves to the diaphragm and via other nerves to chest wall muscles, which collectively contract to expand the lungs. With CSA, the nerve signals are not properly generated for periods of time while the patient is asleep or are of insufficient magnitude to trigger sufficient muscle contraction to achieve inhalation. In either case, the patient thereby fails to inhale until appropriate respiratory nerve signals are eventually generated—at which point fast, deep breathing often occurs (i.e. hyperpnea) to compensate for the increased blood CO2 levels arising due to the episode of CSA. Often, the episodes of CSA are fairly periodic and so periods of apnea alternate with periods of hyperpnea. In other words, CSR occurs.
Therapies can differ significantly depending upon whether the underlying medical condition causing CSR is CHF or is instead CSA. With CHF, drug therapy is preferred, typically centered on medical treatment using angiotensin converting enzyme (ACE) inhibitors, diuretics or digitalis. Cardiac resynchronization therapy (CRT) may also be employed, if a bi-ventricular pacing device is implanted. Briefly, CRT seeks to normalize asynchronous cardiac electrical activation and resultant asynchronous contractions associated with CHF by delivering synchronized pacing stimulus to both ventricles, or to one ventricle upon detection of intrinsic activity in the other ventricle. The stimulus is synchronized so as to help to improve overall cardiac function. This may have the additional beneficial effect of reducing the susceptibility to life-threatening tachyarrhythmias. CRT and related therapies are discussed in, for example, U.S. Pat. No. 6,643,546 to Mathis, et al., entitled “Multi-Electrode Apparatus And Method For Treatment Of Congestive Heart Failure”; U.S. Pat. No. 6,628,988 to Kramer, et al., entitled “Apparatus And Method For Reversal Of Myocardial Remodeling With Electrical Stimulation”; and U.S. Pat. No. 6,512,952 to Stahmann, et al., entitled “Method And Apparatus For Maintaining Synchronized Pacing”. In contrast, to address CSA, an external breathing apparatus, such as a device providing continuous positive airway pressure (CPAP) therapy or bi-level positive pressure therapy (Bi-PAP), is employed. Overdrive pacing may be employed if a pacing device is implanted. Implantable phrenic nerve stimulators may be used as well to maintain inspiration during periods of CSA.
Accordingly, it would be desirable to provide techniques for distinguishing between CHF-induced CSR and CSA-induced CSR, particularly so that appropriate therapies can be exploited, and it is to this end that certain aspects of the invention are directed. Herein, CSR induced by CSA is also referred to as “CSR-CSA”; CSR induced by CHF is also referred to as “CSR-CHF”.
An article entitled “The Entrainment of Low Frequency Breathing Periodicity”, by Millar et al., (CHEST Vol. 98, No. 5, November 1990, pp. 1143–1148) provides data indicating that differences arise in the periodicity of CSR depending up whether CSR-CSA or CSR-CHF. The data suggests that the time period for CSR is higher in CSR-CHF patients than in CSR-CSA patients (or that the frequency of CSR is lower). Although the article does not suggest its exploitation within implantable medical systems, the periodicity of CSR, if properly detected, could potentially be used to distinguish CSR-CSA from CSR-CHF using an implantable medical device and aspects of the invention are directed to that end. Challenges, moreover, remain in determining how best to detect and exploit CSR periodicity within an implantable system for distinguishing CSR-CSA from CSR-CHF. For example, arousal from sleep during CSR can affect the measured periodicity of CSR, thus adversely affecting the viability of any discrimination technique based on CSR periodicity. Accordingly, other aspects of the invention are directed to specific techniques for exploiting CSR periodicity for distinguishing CSR-CSA from CSR-CHF to provide reliable results for use in an implantable system.
Once it has been confirmed that CSR within a patient is induced by CHF, it is desirable to track the severity of CHF, particularly to facilitate selection of appropriate CHF therapies or to titrate such therapies. The article by Millar et al. also provides data indicating that the time period for CSR is correlated with circulation delay within patients (wherein circulation delay was defined as the average time delay for blood to travel from the lungs to a sensor in the carotid artery.) Since a general increase in circulation delay within a patient is likely to be indicative of progression of CHF, the time period for CSR would appear to correlate with the severity of CHF. Although the article does not suggest its exploitation within implantable medical systems, the magnitude of the periodicity of CSR, if properly detected, could potentially be used to track the severity of CHF using an implantable medical device with patients subject to CSR-CHF. Hence, still other aspects of the invention are directed to providing such capability within an implantable system. Again, however, challenges remain in determining how best to detect and exploit the magnitude of the CSR periodicity within an implantable system for tracking the severity of CHF within patients subject to CSR-CHF. As mentioned above, arousal from sleep or other movements occurring during CSR can affect the periodicity of CSR, thus adversely affecting the viability of any CHF tracking technique based on the magnitude of CSR periodicity. Accordingly, still other aspects of the invention are directed to specific techniques for exploiting the magnitude of CSR periodicity for tracking CHF within CSR-CHF patients so as provide reliable results for use in an implantable system.
It is worth noting that others have recognized that frequency and cycle length of CSR may be used to measure the progression of CHF. See, U.S. Patent Application US2002/019367 of Cho et al. However, the patent application of Cho et al. does not appear to provide any indication of how frequency and cycle length are related to progression of CHF. There is no indication, for example, of whether an increase in CSR cycle length indicates that CHF is progressing or whether it is a decrease in CSR cycle length that instead indicates that CHF is progressing. In addition, there does not appear to be any recognition that the CSR within a patient might be the result of CSA rather than CHF or that arousal from sleep or other factors might significantly affect the manner by which frequency and cycle length are evaluated. Accordingly, it does not appear that the patent application to Cho et al. provides a viable system for tracking progression of CHF based on the periodicity of CSR, to which the present invention is directed.